Clinical states with primary or secondary hyperparathyroidism are associated with muscle dysfunction, suggesting that parathyroid hormone (PTH) may affect muscle metabolism. The present study examined the effect of 1-84 PTH and its amino-terminal fragment (1-34 PTH) on energy production, transfer, and utilization by skeletal muscle. Rats weighing 150 to 200 g were injected intraperitoneally with 1-84 or 1-34 PTH, 200 U/day, for 4 days, and control animals received vehicle only. The effect of the simultaneous administration of a calcium channel blocker, verapamil, was examined also. The muscle content of inorganic phosphorus, creatine phosphate, and adenine nucleotides were significantly (P less than 0.01) lower in the PTH-treated rats than in control animals. The hormone significantly reduced mitochondrial oxygen consumption without altering ADP:0 ratio, indicating reduced phosphorylation. Both 1-84 and 1-34 PTH produced significant (P less than 0.01) reduction in the activities of mitochondrial and myofibrillar CPK, and mitochondrial MgATPase. 1-84 PTH reduced the activity of myofibrillar CaATPase as well. There was a significant (P less than 0.01) increment in muscle uptake of 45Ca in the 1-84 PTH-treated rats. Verapamil abolished all the effects of PTH. Our data demonstrate that both 1-84 and 1-34 PTH impair energy production, transfer, and utilization. These biochemical derangements may, at least in part, underlie the myopathy observed in conditions associated with excess PTH.

This study examined the effect of parathyroid hormone (PTH) on myocardial energy production, transfer, and utilization. Rats (150 to 200 g) were injected with 1-84 PTH, 200 U/day i.p., or 1-34 PTH, 200 or 300 U/day i.p., for 4 days. Control animals received the vehicle only. The effect of the simultaneous administration of calcium channel blocker, verapamil, was also examined. Myocardial contents of Pi, ATP, and CP were significantly (P less than 0.01) lower in the 1-84 PTH-treated rats than in control animals. Both 1-84 PTH and 1-34 significantly (P less than 0.01) reduced mitochondrial oxygen consumption without altering ADP:O ratio indicating reduced phosphorylation. 1-84 and 1-34 PTH significantly (P less than 0.01) reduced the activities of mitochondrial and myofibrillar creatine phosphokinase and 1-84 PTH inhibited (P less than 0.01) the activities of mitochondrial Mg ATPase and those of myofibrillar Ca ATPase. There were significant (P less than 0.01) increments in myocardial 45Ca and in total calcium content in 1-84 PTH-treated rats. Verapamil abolished all the effects of 1-84 PTH. Similarly, inactivation of 1-84 PTH abolished its effects. Treatment with 1-84 PTH for 10 days was associated with a significant decrease in cardiac index and mean arterial pressure. Our data demonstrate that both 1-84 and 1-34 PTH impair energy production, transfer, and utilization. These biochemical derangements, if maintained, produce a decrease in cardiac index. It appears that the enhanced entry and the accumulation of calcium in the myocardium, either directly and/or indirectly, are responsible for the action of PTH on energy metabolism of the heart.

The effects of phosphate depletion (PD) of 4, 8, and 12 wk duration on myocardial energy metabolism were studied in rats fed a phosphate-deficient diet and compared with rats pair-fed a normal phosphate diet. Myocardial biopsies were examined for high-energy phosphate bonds. The results show that PD causes a significant reduction in myocardial concentration of inorganic phosphorus at 4 wk of PD and creatine phosphate at 8 wk of PD, while adenine nucleotides were significantly reduced only after 12 wk of PD. The changes in cellular inorganic phosphorus and creatine phosphate displayed a significant correlation with serum phosphorus levels. Mitochondrial respiration was impaired early in PD. Total cellular, mitochondrial, and myofibrillar creatine kinase activities were significantly reduced at 4 wk of PD and fell further at 8 and 12 wk. These data show that chronic PD is associated with reduced mitochondrial capacity to produce ATP, impaired transport via the creatine phosphate shuttle, and reduced myofibrillar ability to utilize ATP. These abnormalities indicate that all steps of myocardial energetics are impaired in PD and provide the molecular basis for the altered myocardial function seen in PD.

The effects of phosphate depletion (PD) of 4, 8, and 12 weeks on skeletal muscle energy metabolism were studied in rats fed a phosphate deficiency diet and compared with rats pairfed with a normal phosphate diet. Skeletal muscle biopsy specimens were examined for energy production, transport, and utilization. The results show that already by 4 weeks of PD, the concentration of inorganic phosphorus of the skeletal muscle was significantly reduced and remained low thereafter. There was significant (P less than 0.01) and direct correlation between the cellular inorganic phosphorus and that of serum phosphorus. Adenine nucleotides, ATP, ADP, AMP, and creatine phosphate levels did not change. Mitochondrial respiration and oxidative phosphorylation were impaired by PD. Total cellular mitochondrial and myofibrillar creatine phosphokinase activities were significantly reduced at 4 weeks of PD and fell further at 8 and 12 weeks. There was a significant (P less than 0.01) and direct correlation between the activity of total extractable creatine phosphokinase and both serum and cellular levels of inorganic phosphorus. These data show that chronic PD is associated with a decrease in energy production, transfer, and utilization by skeletal muscle and provides information on the molecular events responsible for the myopathy of PD.

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